High grade squamous intraepithelial lesion on high‐risk HPV negative patients: Why we still need the Pap test

Abstract

Background Cervical cancer is caused by high‐risk human papillomavirus (hrHPV). Though screening Pap test (PT) has reduced cancer mortality by detecting precursor lesions, there is now a move toward replacing screening PT with hrHPV testing. The aims of this study were to determine hrHPV negative rate in high grade squamous intraepithelial lesion (HSIL) PT in high‐risk patients and correlate with histopathology; and to review the hrHPV negative HSIL PT. Method LIS was searched (January 2015–June 2016) for HSIL PT results. Patient chart was reviewed for age, hrHPV co‐testing result including genotyping (Aptima®), and histopathology follow‐up (f/u) which was compared between hrHPV‐positive and hrHPV‐negative groups. hrHPV‐negative HSIL PT slides were re‐evaluated for concordance with original interpretation. Student t test was used for data analysis. Results There were 230 patients with HSIL PT who had hrHPV co‐testing and 199/230 had histopathological f/u. Majority (210/230, 91.3%) were hrHPV positive, and 20 (8.7%) were hrHPV negative. HrHPV negative HSIL was significantly more common in older women (mean age 49.3 years) compared with hrHPV‐positive HSIL (mean age 40.7 years) (P = .0015). The most frequently detected genotype was HPV16 (40%). F/u was CIN2/3 in 145/181 (80%) hrHPV‐positive HSIL (includes nine squamous cell carcinoma) and 6/16 (37.5%) hrHPV‐negative HSIL. Conclusion Although the risk of CIN2/3 and carcinoma was higher in hrHPV‐positive patients, possibility of hrHPV‐negative dysplastic lesions should be considered in older women as 6 of 16 (37.5%) of these women had CIN2/3 and/or carcinoma which would have been missed without the PT.

Age-Related Changes in the Fraction of Cervical Intraepithelial Neoplasia Grade 3 Related to HPV Genotypes Included in the Nonavalent Vaccine

“…Based on these results, it would be interesting to ask the question about the need to use a cotesting (Pap smear + HPV test) at a given age cutoff. In a recent paper, Sun et al showed that about 40% of older women with CIN2+ and carcinoma had a negative hr-HPV test, and these cases would have been missed without using the Pap test [23].…”

Computational Cytology: Lessons Learned from Pap Test Computer-Assisted Screening

“…These practice changes have significantly reduced the number of Pap tests performed and suggest that the number of Pap tests may be further reduced by future iterations of clinical management guidelines, particularly in the HPV-vaccinated population [50]. However, it is important to note that up to 9% of patients with a negative HPV test can still have subsequent HSIL on biopsy [51]. As such, morphologic evaluation is still an important component of ensuring optimal patient care.…”

Cotesting in Cervical Cancer Screening

“…In one study, more than 1 in 3 women who had CIN 2 or 3 and/or carcinoma would have been missed without the Pap cytology. 5 In another study, more than half of the women with CIN 2+ lesions including cervical cancer had a positive Pap test and negative HPV testing. 6 Regarding costs, Felix et al examined cost-benefit and found that, compared with primary HPV screening, cotesting both saved lives and was cost-effective.…”